Tributylphosphine → 4-((5-Chloro-2-thienyl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203031노트

반응식

HRID 2203031 반응식
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:15]=[C:14]([CH:16]4[CH2:18][CH:17]4[C:19]([OH:22])([CH3:21])[CH3:20])[N:13]([CH3:23])[C:12]=3[CH:24]=2)[C:4](=[O:25])[CH:3]=1.[Cl:26][C:27]1[S:31][C:30]([CH2:32]O)=[CH:29][CH:28]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[Cl:26][C:27]1[S:31][C:30]([CH2:32][O:1][C:2]2[CH:7]=[CH:6][N:5]([C:8]3[CH:9]=[CH:10][C:11]4[N:15]=[C:14]([CH:16]5[CH2:18][CH:17]5[C:19]([OH:22])([CH3:20])[CH3:21])[N:13]([CH3:23])[C:12]=4[CH:24]=3)[C:4](=[O:25])[CH:3]=2)=[CH:29][CH:28]=1

참가 물질

6

반응물 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 12554178(5-Chlorothiophen-2-yl)methanolHCID 1213862594-Hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

생성물 1

HCID 897025734-((5-Chloro-2-thienyl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one수율 21%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
60 °C

실험 절차

To a mixture of 4-hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (100 mg), (5-chloro-2-thienyl)methanol (88 mg), tributylphosphine (0.219 ml) and THF (10 ml) was added 1,1′-(azodicarbonyl)dipiperidine (223 mg), and the mixture was stirred at 60° C. for 2 h. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by NH silica gel column chromatography (EtOAc/MeOH), followed by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH). The resulting solid was recrystallized from IPE-IPA to give the title compound (29.1 mg) as an off-white solid.

후처리

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. washthe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by NH silica gel column chromatography (EtOAc/MeOH)
  6. customThe resulting solid was recrystallized from IPE-IPA

출처 및 근거

ORD 기록
ord-95333d0b1ba3423d8d880c5d325886ec
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365540B2

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